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Studies on the Enzyme Reaction Mechanism of Cytochrome P450

细胞色素P450酶反应机制的研究

基本信息

批准号：
59470118
负责人：
HIROBE Masaaki
金额：
$ 4.8万
依托单位：
Faculty of Pharmaceutical Sciences, University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59470118/
关键词：
Cytochrome P450 FeTPPCl Electron Transfer Effector Oxygenase Biomimetic Reaction Flavin

项目摘要

Cytochrome P450 and its electron transfer system play an important role in metabolizing biomolecules and xenobiotics. The P450 enzyme catalyzes the oxidation of various substrates by the introduction of one oxygen atom into a substrate from dioxygen. Our research projects concerning the oxidation system are shown below.(1) Much interests have been focused on the mechanism of the electron transfer between the flavin and the heme. Hence, intramolecular linked flavin- porphyrin complexes have been prepared to elucidate the flavin-heme electron transfer and its transient nature. Furthermore, N-benzyl-1,4- dihydronicotinamide compounds have been synthesized as the model of NAD(P)H coenzyme. Then, the steric and electronic effects have been discussed based on UV spectra and redox potential data.(2) P450 enzyme model systems have been studied to reveal the enzyme mechanism of P450. Furthermore, polypeptide-bound Fe(III)TPPCl has been prepared to consider environmental effects of protein around hemin in P450.(3) In cytochrome P450 monooxygenations, metalloporphyrin oxenoid complex is considered to be an ultimate reactive species which is responsible for the oxidation of substrates. In the research, the formation mechanism of the metalloporphyrin oxenoid via acylperoxy metalloporphyrin was proposed.

细胞色素P450及其电子传递系统在生物分子和外源生物代谢中起着重要作用。P450酶通过将一个氧原子从二氧引入到一个底物中来催化各种底物的氧化。我们关于氧化系统的研究项目如下所示。(1)黄素与血红素之间的电子传递机制一直是人们关注的焦点。因此，制备了分子内连接的黄素-卟啉配合物，以阐明黄素-血红素的电子转移及其瞬态性质。此外，还合成了n -苄基-1,4-二氢烟酰胺类化合物作为NAD(P)H辅酶的模型。然后，根据紫外光谱和氧化还原电位数据，讨论了空间位阻效应和电子效应。(2) P450酶模型系统的研究揭示了P450的酶机制。此外，制备了多肽结合的Fe(III)TPPCl，以考虑P450中血红蛋白周围蛋白的环境效应。(3)在细胞色素P450单氧作用中，类金属卟啉络合物被认为是负责底物氧化的最终反应物质。在研究中，提出了酰基过氧型金属卟啉形成类金属卟啉的机理。